Effects of outcome expectancies and disinhibition on ad lib alcohol consumption

CD95 ligand (CD95L) potently induces apoptosis by activating CD95 on target cells. It has recently been reported that melanoma cells in vivo express a significant amount of CD95L, thereby being immediately able to kill CD95-bearing immunocompetent cells specific for cancer antigens, which infiltrate the lesions. In this study, we employed immunohistochemistry using an antibody directed against CD95L to investigate at which stage the melanoma CD95L expression is turned on. Skin biopsies of 49 lesions from 46 patients were assessed. These included benign and dysplastic naevi, melanoma in situ, stage I melanomas (Clark's level 2 or 3), advance-phase melanomas (Clark's level 4 or 5) and lymph node metastases. CD95L was expressed in all of the advance-phase melanomas as well as lymph node metastases of cutaneous origin, whereas neither melanoma in situ, benign naevi nor dysplastic naevi reacted positively with the antibody. To investigate a link between positivity and tumour size, the data were analysed on the basis of Breslow thickness, and indicated that expression was observed only when tumours were thicker than 0.75 mm. We next compared expression of CD95L and HMB-45. CD95L was positive only in melanomas in a more advanced phase than stage I, whereas HMB-45 was not only expressed in melanoma cells but also in benign pigmented naevi. This indicated the advantage of CD95L staining to diagnose melanoma. The present study indicates the significant correlation between tumorigenicity and expression of CD95L, and thereby raises the possibility that CD95L may be a useful diagnostic marker for malignant melanomas.     

Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group

PURPOSE: Patients with primary cutaneous melanoma with a Breslow thickness > or = 1.5 mm have only a 30% to 70% probability of survival after surgery, and no adjuvant therapy has so far improved this outcome. Since interferon alfa-2a (IFNalpha2a) exhibits antitumor activity in metastatic melanoma, we investigated whether adjuvant IFNalpha2a diminishes the occurrence of metastases and thus prolongs disease-free survival in melanoma patients after excision of the primary tumor. PATIENTS AND METHODS: In a prospective randomized study, 311 melanoma patients with a Breslow thickness > or = 1.5 mm were assigned to either adjuvant IFNalpha2a treatment (n = 154) or observation (n = 157) after excision of the primary tumor. IFNalpha2a was given daily at a dose of 3 mIU subcutaneously (s.c.) for 3 weeks (induction phase), after which a dose of 3 mIU s.c. three times per week was given over 1 year (maintenance phase). RESULTS: Prolonged disease-free survival was observed in patients treated with IFNalpha2a versus those who underwent surgery alone. This difference was significant (P = .02) for all patients enrolled onto the study (intention-to-treat analysis) at a mean observation time of 41 months. Subgroup analysis showed that Breslow tumor thickness had no influence on treatment results in the groups of patients investigated. CONCLUSION: Adjuvant IFNalpha2a treatment diminishes the occurrence of metastases and thus prolongs disease-free survival in resected primary stage II cutaneous melanoma patients.     

2nd revised consensus skin melanoma. De Nederlandse Melanoom Werkgroep]

The 'Guideline melanoma of the skin, second revised consensus' was published in March 1997. Some of the contents are cited: Over 1600 new melanomas are diagnosed in the Netherlands each year; by now the mean 5-year survival amounts to over 80%. In examination of a pigmented lesion a dermatoscope is a valuable tool. The recommended margin of the diagnostic excision was reduced from 5 mm to 2 mm of macroscopically normal skin round the lesion; the margins in definite excision are: 1 cm of normal skin for a Breslow thickness < or = 2 mm; 2 cm for a Breslow thickness > 2 and < or = 4 mm. A margin of at least 2 cm seems also justified for thicker melanomas. Elective (prophylactic) regional lymph node dissection is advised against. Sentinel node biopsy appears to be an attractive method to detect occult metastasis in regional nodes. In lymph node metastasis a (therapeutic) regional lymph node dissection should be performed. In case of inoperable tumourgrowth in an extremity regional isolated perfusion is indicated. Radiotherapy may be applied curatively (e.g. if surgery is not possible), palliatively (if desired in combination with hyperthermia) or postoperatively (if non-radical resection is suspected). Adjuvant systemic therapy in melanoma patients is still experimental; the earliest results of high doses of interferon alpha are encouraging. Atypical (dysplastic) naevi and congenital naevi are important risk factors for melanoma. No consensus was reached regarding prophylactic removal of all congenital naevi. Regarding the duration of the follow-up period, 5 years suffices in patients with a melanoma with a Breslow thickness < or = 1.5 mm (provided there are no histological signs of regression), while 10 years is required for melanomas with a Breslow thickness > 1.5 mm. The patient should be actively involved in the follow-up (inspection, palpation). Routine blood testing, roentgen examination or ultrasonography are considered to be useless. There are no indications that hormonal alterations during pregnancy or use of the pill stimulate the growth of micrometastases that may be present. Excessive exposure to ultraviolet rays is discouraged.     

Does palpability of primary cutaneous melanoma predict dermal invasion?

BACKGROUND: Relatively few studies have addressed the question of whether clinical estimation of melanoma thickness by palpation can accurately predict its histologic thickness. If palpability was a reliable predictor of dermal invasion, it could be used to define the surgical margin. OBJECTIVE: We sought to determine whether clinical elevation of melanoma could be used to predict the presence or absence and the degree of dermal invasion in patients with stage 1 cutaneous melanoma. METHODS: Melanomas in 165 patients were categorized by one observer as flat, just palpable, palpable, or nodular. This was compared with histologic measurements of tumor thickness. RESULTS: Overall there was significant correlation between the degree of palpability of melanoma and the presence or absence of dermal invasion (p<0.001), Breslow thickness (p<0.0001), and Clark level (p<0.001). However, the relation between palpability and Breslow thickness for invasive melanomas less than 1 mm thick was weaker (n=62, p=0.053), and the correlation between elevation and Clark level was not significant for invasive melanomas less than 4 mm thick (n=111, p>0.999). CONCLUSION: We conclude that palpability of melanoma is an inadequate guide to the presence or absence and degree of dermal invasion in melanomas less than 1 mm thick and cannot be used to determine the surgical margin.     

Desmoplastic and desmoplastic neurotropic melanoma: experience with 280 patients

BACKGROUND: It has been suggested that desmoplastic melanoma (DM) and desmoplastic neurotropic melanoma (DNM) are associated with worse prognoses and higher local recurrence rates than other forms of melanoma. In the current study, a large series of patients with DM and DNM treated at a tertiary referral center was reviewed. METHODS: For 190 patients with DM and 90 patients with DNM accrued over a 10-year period, clinical features were recorded and all available histopathology was reviewed. The associations between clinical and pathologic variables, biologic behavior, and eventual outcome were analyzed. RESULTS: The male-to-female ratio was 1.75:1 and the median patient age 61 years. The median tumor thickness was 2.5 mm, and 44% of cases were amelanotic. Five-year survival was 75%. Significant predictors of overall survival were a high mitotic rate (P=0.003) and tumor thickness (P=0.011). All the DNMs exceeded 1.5 mm in thickness and were graded as Clark's level IV or V. There was a significant increase in local recurrence when neurotropism was present (P < 0.001). The rate of local recurrence was not higher for DM than for other cutaneous melanomas. CONCLUSIONS: There was no statistically significant difference in survival for patients with DM and those with DNM, and overall survival for both was similar to that for patients with other cutaneous melanomas. However, there was a lower rate of regional lymph node metastasis at initial presentation and as the first recurrence for both DM and DNM. The local recurrence rate was higher when the surgical clearance margin was <1 cm and when neurotropism was present.     

Desmoplasia and neurotropism. Prognostic variables in patients with stage I melanoma

BACKGROUND: Desmoplastic melanomas with and without neurotropism are thought to be more clinically aggressive than other melanomas of comparable thickness. This study evaluates the prognostic significance of desmoplasia and neurotropism in Patients with Stage I cutaneous melanoma completely excised at the initial presentation of disease and prospectively studied for a minimum of 8 years. METHODS: Desmoplasia and neurotropism were evaluated as single prognostic predictors in survival outcome of cutaneous Stage I melanomas and as variables in the University of Pennsylvania Pigmented Lesion Study Group 8-year survival model for Stage I melanoma. In addition, the clinical presentation and follow-up of melanomas with desmoplasia and/or neurotropism was compared with that of other types of cutaneous Stage I melanoma in patients also followed for a minimum of 8 years. RESULTS: Neurotropism was associated with a statistically significant decrease in survival in patients with melanomas with desmoplasia. A decrease in survival also was observed in other types of melanoma with neurotropism, but the difference was not statistically significant. Melanomas with neurotropism had a statistically significant increase in local recurrence. Desmoplasia was not associated with a statistically significant decrease in survival. CONCLUSION: Desmoplasia is not associated with a statistically significant decrease in the prognosis of patients with primary cutaneous Stage I melanoma. The more clinically aggressive behavior of desmoplastic melanomas observed in previous studies may be secondary to initial misdiagnosis and/or inadequate margin assessment of these lesions. Neurotropism, however, is associated with a statistically significant decrease in survival in patients with desmoplastic melanomas and is most likely associated with decreased reduces patient survival in other melanoma types. Neurotropism is also related to an increase in the frequency of local recurrence of melanoma.     

Survival analysis in patients with cutaneous malignant melanoma

INTRODUCTION: Cutaneous malignant melanoma (MM) takes only 3% of all malignant tumours of the skin, but for reason of its increased frequency and pronounced tendency to rapid growth and metastases, it causes 60% of total lethal outcomes due to malignant tumours of the skin [1]. Primary MM is a diagnostic problem because of the great variety of its clinical features. Asymmetric configuration, irregular border, speckled color(r)diameter of more than 6 mm, and elevation of the surface, suggest suspicion of malignant alteration, but even then misdiagnosis is possible. For the final diagnosis of MM histopathological confirmation is necessary. The method to use is the extensive excisional biopsy of the lesion and its borders [2]. Histopathological diagnosis is based on microscopic findings which include: histogenetic type of MM, tumour thickness according to Breslow, level of invasion according to Clark, presence of ulceration, grade of lymphocyte infiltration, mitote rate, type of cells, presence of melanin in cells [2, 3]. PATIENTS AND METHODS: A five-year survival of patients with cutaneous malignant melanoma (MM) was studied according to sex, age and distinct features of the tumour: site, type of initial therapy, stage of the disease, time from the first signs of the disease to diagnosis of MM, histological findings (histogenetic type, Breslow's tumour thickness, Clark's level of invasion, presence of ulceration, degree of lymphocyte infiltration, number of mitoses, type of cells, intensity of pigmentation) and presence of metastases. The retrospective study included 336 patients with cutaneous MM. There were 185 female (55.1%) and 151 male patients (44.9%), aged 14-83 years, mean age 48.8 years, who were treated at the institute of Oncology and Radiology in Belgrade from 1978 to 1990. The mean follow-up was 60 months (1-144 months). Melanoma in situ had 16 (4.1%) patients. Stage I had 45 patients (14.1%), stage II 163 (48.5%), stage III 83 (24.7%) and stage IV 29 (8.6%) patients. Acral location on hands and feet had 40 (11.9%) patients, on head and neck 36 (10.7%), on the trunk 146 (43.5%) and on the extremities (except hands and feet) 114 (33.9%) patients. Nodular melanoma (NM) was the most frequent histogenetic type revealed in 150 (44.6%) patients, superficial spreading melanoma (SSM) in 105 (31.1%) patients, acral melanoma (AM) in 39 (11.5%) and lentigo malignant melanoma (LMM) in 32 (9.4%) patients (Table 1). Five-year survival rate was calculated according to Kaplan-Meier's method and significance of the difference between some categories was tested by Long-Rank's test; the significance less than 0.05 was accepted. RESULTS: Statistically highly significant differences in a five-year survival (p < 0.01) were related to sex p = 0.0005, age p = 0.0017, tumour site p = 0.0025, initial therapy p = 0.0036, stage of MM p = 0.0000, histological features of the tumour p = 0.0000 and presence of metastases p = 0.0000. A better five-year survival prognosis was found in female patients (64.5%) compared to male patients 44.5%, aged 27-46 years (87.3%) compared to patients younger than 26 years (43.5%); patients with melanoma on the extremities (except hands and feet) had a better five-year survival (66.7%) compared to patients younger than 26 years (43.5%); patients with melanoma on the extremities (except hands and feet) had a better five-year survival (65.7%) compared to patients with melanoma on the trunk or acral melanoma (47.3%). Higher survival was recorded in the group of patients with the tumour 1.5-3 mm thick, in whom the tumours was excised and regional nodes dissected as the primary therapy (66.9%) compared to those who underwent excision of the tumor only (48.8%). A five-year survival of patients with MM in situ was 100% for those in stage I; 85% in stage II; 42% in stage III, 16% and 0% in stage IV. The patients in whom the diagnosis of MM was established within 10 months after the first signs of the disease had significa     

Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma

BACKGROUND: Primary cutaneous melanoma is often infiltrated lymphocytes that provide the opportunity to study what may be the local immunologic reaction to the tumor and to correlate the presence of these lymphocytes with overall survival. In an attempt to delineate the histologic diagnostic criteria, to classify different categories of lymphocytic infiltrates, previously described by Elder et al. at brisk, nonbrisk, and absent, and to verify their prognostic significance, we reviewed 285 consecutive cases of primary cutaneous melanomas (American Joint Committee on Cancer Stage I and II). METHODS: In addition to clinical variables (age, sex, and location of tumor) and the presence of tumor infiltrating lymphocytes in the vertical growth phase, the histopathologic attributes reviewed included mitotic rate, thickness, and regression. The results were derived from independent histopathologic review by two pathologists (C.G.C., M.C.M., Jr.) on separate occasions. A multivariate analysis of survival was performed with the Cox's regression model. RESULTS: The 5- and 10-year rates for melanoma with a vertical growth phase and a brisk infiltrate were 77% and 55%, respectively. For tumors with a nonbrisk infiltrate, the 5- and 10-year survival rates were 53% and 45%, respectively, and for tumors with absent tumor infiltrating lymphocytes, the 5- and 10-year survival rates were 37% and 27%, respectively. Mitotic index, thickness, and tumor infiltrating lymphocytes were statistically (univariate analysis) significant prognostic factors (P = 0.003, 0.000001, 0.0003, respectively), whereas the presence or absence of regression is not. In the univariate statistical analysis, the sex of patients and site of melanoma also were statistically significant (P = 0.00001 and 0.002 respectively), whereas age (P = 0.98) was not statistically significant. The multivariate analysis of thickness, mitotic rate, and tumor infiltrating lymphocytes showed that thickness and presence tumor infiltrating lymphocytes were significant and independent histologic prognostic factors. With regard to the clinical factors, sex retained its independent prognostic significance. The histologic characteristics of melanoma with vertical growth phase (brisk, nonbrisk, and absent) are exemplified. CONCLUSIONS: We demonstrated that when categories of tumor infiltrating lymphocytes are strictly defined, they indeed have very strong predictive value for primary cutaneous melanomas with a vertical growth phase. This work confirms the work of Clark et al. and fully illustrates the brisk, nonbrisk, and absent categories of infiltration. Finally, a multivariate analysis comparing thickness, mitotic rate and presence of tumor infiltrating lymphocytes showed that only thickness and presence of tumor infiltrating lymphocytes are significant and independent positive histologic prognostic factors.     

Survival following breast-conserving surgery and irradiation or modified radical mastectomy in patients with invasive breast cancers with a maximum diameter of 1 cm

The reported relapse-free survival for women with invasive breast cancers measuring no more than 10 mm in dimension ranges from 75% to 95%, with axillary status an important prognostic factor in most series. Further study of prognostic variables in this most favorable subset is notably limited. We retrospectively reviewed the records of 168 women with invasive breast cancers < or = 10 mm treated with either breast conserving surgery+axillary dissection (AXD) and radiation therapy, or mastectomy+AXD. The actuarial survival and survival free of distant metastases (DMFS) at 7 years was 95% and 97%, respectively. Location and size of the primary tumor were most important in predicting outcome, although statistical significance was not achieved. The 5-year distant metastases-free survival (DMFS) was 100% for central and inner quadrant tumors, compared to 97% in those with outer quadrant tumors, p = 0.18. The 5-year DMFS was 100%, 95%, and 98% for patients with cancers 2-5 mm, 6-9 mm, and 10 mm, respectively, p = 0.15. Status of the axillary lymph nodes, type of breast surgery, clinical tumor status (palpable vs. nonpalpable), age, menopausal status, histologic grade, systemic therapy, or histologic type were not found to have a significant impact on prognosis.     

Surgical management of aberrant sentinel lymph node drainage in cutaneous melanoma

BACKGROUND: Sentinel lymph node (SLN) mapping by lymphoscintigraphy has changed the surgical management of regional lymph node metastases for melanoma. SLNs lying outside of traditional nodal basins are now being identified. Our hypothesis is that when preoperative lymphoscintigraphy identifies aberrant SLNs, these nodes should be excised and, if histologically positive, lymphadenectomy of the aberrant nodal basin should be performed. METHODS: Patients with melanomas 1 mm or larger Breslow thickness and clinical stage N0M0 underwent lymphoscintigraphy and excision with SLN biopsy. Preoperative lymphoscintigraphy, intraoperative gamma probe, and intraoperative injection of isosulfan blue were performed to identify the SLN. Aberrant SLNs were defined as epitrochlear, supraclavicular, or popliteal nodes for extremity lesions and intramuscular nodes for truncal and head and neck lesions. RESULTS: Thirty-two patients were entered into the protocol. Seven (22%) were found to have aberrant nodes. Five of 19 patients with extremity melanoma had an aberrant SLN; 2 of 13 patients with truncal and head and neck melanoma had an aberrant SLN. CONCLUSIONS: This study demonstrates that (1) aberrant SLNs are encountered with similar frequency for extremity and truncal lesions, (2) biopsy should be performed on aberrant SLNs with intraoperative lymph node mapping with the gamma probe and blue dye, and (3) lymphadenectomy of the aberrant region should be considered if the aberrant SLN is positive.     

Pelvic exenteration for malignant melanomas of the vagina or urethra with over 3 mm of invasion

Pelvic exenteration has usually been employed as salvage treatment for gynecologic malignancies which have failed primary radiotherapy. The therapeutic mainstay for vulvar melanomas has become wide local excision with or without concurrent regional node dissection. Patients with primary melanoma of the vagina who undergo exenteration as primary therapy may experience 50% 5-year survival if the pelvic nodes are free of metastases. However, the overall 5-year survival for vaginal melanoma is 15%. In our patient population, there have been four patients with vaginal or urethral melanomas treated primarily with pelvic exenteration. The purpose of this study was to report that patients with vaginal or urethral melanomas over 3 mm in thickness may benefit from primary pelvic exenteration. Four patients underwent pelvic exenteration at Indiana University Medical Center for malignant melanoma of the vagina or urethra between 1986 and 1992. The pathologic specimens of all patients were analyzed for thickness, growth pattern, and nodal metastases. Patient age ranged from 50 to 71. Thickness of the melanomas ranged from > 3 to 12 mm. All four patients underwent exenterations, three total and one anterior. All patients had negative pelvic and inguinal nodes at the time of surgery. None of the patients has experienced a recurrence. Three of four patients are alive without evidence of disease at 31 to 97 months following their exenteration. One patient died postoperatively of cardiopulmonary complications. Patients with melanomas of the vagina and female urethra, greater than 3 mm in thickness, may benefit from primary pelvic exenteration.     

Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger

OBJECTIVE: A prospective multi-institutional randomized surgical trial involving 740 stage I and II melanoma patients was conducted by the Intergroup Melanoma Surgical Program to determine whether elective (immediate) lymph node dissection (ELND) for intermediate-thickness melanoma (1-4 mm) improves survival rates compared with clinical observation of the lymph nodes. A second objective was to define subgroups of melanoma patients who would have a higher survival with ELND. METHODS: The eligible patients were stratified according to tumor thickness, anatomic site, and ulceration, and then were prerandomized to either ELND or nodal observation. Femoral, axillary, or modified neck dissections were performed using standardized surgical guidelines. RESULTS: The median follow-up was 7.4 years. A multifactorial (Cox regression) analysis showed that the following factors independently influenced survival: tumor ulceration, trunk site, tumor thickness, and patient age. Surgical treatment results were first compared based on randomized intent. Overall 5-year survival was not significantly different for patients who received ELND or nodal observation. However, the 552 patients 60 years of age or younger (75% of total group) with ELND has a significantly better 5-year survival. Among these patients, 5-year survival was better with ELND versus nodal observation for the 335 patients with tumors 1 to 2 mm thick, the 403 patients without tumor ulceration, and the 284 patients with tumors 1 to 2 mm thick and no ulceration. In contrast, patients older than 60 years of age who had ELND actually had a lower survival trend than those who had nodal observation. When survival rates were compared based on treatment actually received (i.e., including crossover patients), the patients with significantly improved 5-year survival rates after ELND included those with tumors 1 to 2 mm thick, those without tumor ulceration, and those 60 years of age or younger with tumors 1 to 2 mm thick or without ulceration. CONCLUSION: This is the first randomized study to prove the value of surgical treatment for clinically occult regional metastases. Patients 60 years or age or younger with intermediate-thickness melanomas, especially with nonulcerative melanoma and those with tumors 1 to 2 mm thick, may benefit from ELND. However, because some patients still are developing distant disease, these results should be considered an interim analysis.     

Heterogeneous expression of immunotherapy candidate proteins gp100, MART-1, and tyrosinase in human melanoma cell lines and in human melanocytic lesions

In recent years, it has become evident that T cells can recognize peptides of melanocytic lineage antigens such as gp100, MART-1, and tyrosinase at the tumor cell surface and can subsequently destroy these cells. It is thus feasible to develop immunotherapeutic approaches based on the melanocytic marker profiles of melanoma cells. One of the predictors of the success rate of such a treatment is the extent of positive (target) tumor cells within the lesions of the patient. First, we investigated the presence of these three proteins in 18 human melanoma cell lines using RT-PCR and immunohistochemistry. In 11 cell lines, mRNA and protein of all three markers could be detected; in one cell line, only two markers were present, and six melanoma cell lines showed no evidence for these markers. Secondly, we stained frozen sections of 105 human melanocytic lesions, 13 common nevocellular nevi, 13 atypical nevi, 13 early primary melanomas (Breslow < 1.5 mm), 25 advanced primary melanomas (aPM; Breslow > or =1.5 mm), and 41 melanoma metastases (MM) with antibodies against glycoprotein 100, melanoma antigen recognized by T cells, and tyrosinase. In addition, we used the 3,4-dihydroxy-L-phenylalanine reaction to detect tyrosinase enzyme activity as a confirmation of the tyrosinase immunohistochemical results in a subset of the lesions. In the benign lesions, glycoprotein 100 was more prominently expressed in epidermal melanocytes, whereas melanoma antigen recognized by T cells was encountered in all or nearly all dermal melanocytes in all nevocellular nevi and atypical nevus lesions. Tyrosinase was found in a lower percentage of melanocytes, both in the epidermis and in the dermis within these lesions. With regard to heterogeneity of staining within the malignant lesions, we found that 54% (early primary melanomas), 48% (aPMs), and 56% (MM) of the lesions stained within the same staining category for all three proteins studied. Approximately 17% of the aPM and MM lesions did not show positive tumor cells for any of the three proteins. We conclude that a subgroup of patients with high expression should be selected for immunotherapeutic treatment approaches based on the presence of these proteins.     

Relative importance of quantifying area and vascular patterns in uveal melanomas

PURPOSE: To test whether the cross-sectional area of choroidal and ciliary body melanomas and quantification of microcirculatory networks and parallel vessels with cross-linking are features associated with death from metastatic melanoma, and to compare new with conventional histologic prognostic features. METHODS: The cross-sectional area of 234 ciliary body or choroidal melanomas was measured from digitized images of histologic sections. The percentage of cross-sectional area occupied by two microcirculatory patterns-networks and parallel vessels with cross-linking-was calculated for the 152 tumors containing at least one focus of either pattern. Kaplan-Meier survival curves were generated based on cross-sectional and percentage of cross-sectional areas of these patterns. Cox proportional hazard regression methods related time to death from melanoma with sets of predictor variables. For each model, percent variation explained was computed. RESULTS: Patient survival differs significantly when tumors are classified based on cross-sectional area: small (<16 mm2), medium (> or =16 mm2 but <61.4 mm2), and large (> or =61.4 mm2). Patients with tumors containing networks and parallel vessels with cross-linking microcirculation patterns that occupy 2% of cross-sectional area have a significantly worse prognosis than do those patients with tumors containing a smaller percentage of these patterns. CONCLUSIONS: Quantifying cross-sectional tumor area and the percentage area occupied by networks and parallel vessels with cross-linking microcirculatory patterns in ciliary body and cho. roidal melanomas provides significant prognostic information. Compared with more conventional prognostic characteristics, the most dramatic increase in prognostic information is provided by determination of the presence or absence of microvascular patterns.     

Management of cutaneous melanoma M0: state of the art and trends

This article reviews the epidemiology, diagnosis and treatment of cutaneous melanoma, including the most recent developments. The combination of positive family history, fair complexion, number of nevi, exposure to sun and/or chromosomal alterations seem to be implicated in the pathogenesis of cutaneous melanoma. Melanomas can be classified according to their growth patterns, and tumour microstaging is of straightforward predictive value for survival and risk of metastasis, although new factors are also being investigated. As yet, surgical excision is the only effective treatment available for primary tumours, resection margins varying according to tumour thickness. Elective node dissection is, however, no longer advocated for melanomas thinner than 1.5 mm, and there is disagreement as to its role for thicker lesions. In contrast, selective node dissection at the time of definitive surgery is becoming more widely accepted, with regional node dissection being restricted to positive cases. Therapeutic dissection is required for lymph node involvement, the most common pattern of recurrence from melanoma, which affects nearly 30% of all patients. Complete remission rates from isolated limb perfusion, which has been employed in patients with multiple recurrences or in-transit metastases, range from 40 to 90%, depending on drugs and techniques used in different series; the best responses so far have been obtained with tumour necrosis factor in combination with melphalan. Patients with thick lesions (> 4 mm) or lymph node metastases have a high risk of micrometastases that would warrant adjuvant therapy. The only agent found to affect survival is interferon alpha-2.     

Limited plasticity of human muscle

Incision biopsy of skin melanoma is performed after forming a circular blocking barrier by means of a laser beam. Once tumor proper is subsequently irradiated, this prevents dissemination of tumor process. Skin melanomas, degree I-IV invasion (Clark), and 4.5 mm thick (Breslow) are effectively treated by pulsed laser radiation.     

Protein expression of the cell-cycle inhibitor p27Kip1 in malignant melanoma: inverse correlation with disease-free survival

In the present study we analyzed, by immunohistochemistry, a panel of human melanomas for protein expression of the cyclin-dependent kinase (cdk) inhibitor p27Kip1 and evaluated whether deregulated expression correlates with clinical outcome for this type of cancer. We found that p27Kip1 was strongly expressed by normal melanocytes and benign nevi, whereas in malignant melanoma, a heterogeneous expression pattern was observed. In the case of nodular melanomas, the level of p27Kip1 was found to correlate significantly with the thickness of the tumor, with less protein expressed in thicker lesions. We also found that patients having tumors with fewer than 5% p27Kip1-staining cells had a significantly higher risk of early relapse of their disease compared with those expressing moderate or high levels. In contrast, the level of p27Kip1 did not correlate with tumor thickness or disease-free survival in patients with superficial spreading melanomas, suggesting that p27Kip1 may play different roles in these two major pathological subgroups of malignant melanoma. Furthermore, p27Kip1 did not appear to have an influence on overall survival for either subgroup. When we examined the combined effect of p21WAF1/CIP1 (another cdk inhibitor) and p27Kip1 on clinical outcome, we found that analysis of these two cdk inhibitors together may have greater prognostic potential than either alone. In conclusion, our results suggest that virtually complete loss of p27Kip1 protein expression has potential importance as a prognostic indicator of early relapse in patients with nodular melanoma The results, furthermore, underscore the value of analyzing multiple cell cycle regulatory proteins to obtain the most reliable indication of prognosis.